After 100 Years, Alzheimer's Still Somewhat a Mystery

If I turned back the clock 100 years to Nov. 3, 1906, and happened to be sitting, surrounded by psychiatrists in a small stone auditorium in the village of Tubingen, Germany, I might see on the program the name of a speaker, Dr. Alois Alzheimer.

Alzheimer actually spoke in this German auditorium in 1906, and he described a patient named "Augusta" who, in her middle 50s, had developed the seemingly unfounded delusion that her husband was unfaithful.

This delusion blossomed into full-fledged paranoid psychosis, and Alzheimer continued to care for Augusta in the hospital until she died.

Alzheimer then personally conducted her autopsy.

During the autopsy, he noticed something very wrong with Augusta's brain, which he called "a peculiar disease of the cerebral cortex."

Alzheimer used that phrase as the title of his presentation at Tubingen.

He had thought, at the time, that Augusta's "peculiar disease" was a rarity.

But, in fact, half of our current population older than the age of 85 is affected by the same disease.

Today, we call it Alzheimer's disease.

Alzheimer might be astonished to learn that nursing homes and psychiatric hospitals in developed nations have gradually filled with millions of patients suffering from the still-baffling illness that now carries his name.

A Slow Discovery

Doctors didn't often use the diagnosis of Alzheimer's disease until very recently.

The syndrome of dementia -- literally, the loss of the ability to think or mentate -- was long blamed on the narrowing of blood vessels in the brain, but the narrowing blood vessels weren't severe enough to explain the problems with thought and reasoning.

Over time, though, medicine evolved and people lived longer.

As life span increased, and as the brains of our elders began to be examined, two things happened.

First, highly functional 80- and 90-year-olds -- think pianist Vladimir Horowitz or cellist Pablo Casals -- defied the myth that late-life brain failure was inevitable; in other words, dementia wasn't something that "normally" happened, doctors realized.

Then, by comparing patients' medical histories with their autopsies, doctors realized that the brains from most elderly patients with dementia were "gunked up" with abnormal proteinlike structures, both inside and outside nerve cells.

That gunk between nerve cells, called amyloid plaque, is now considered one sign of Alzheimer's disease.

So, doctors gradually began to recognize the disease, but the truth is, doctors aren't certain that these plaques cause Alzheimer's disease, and doctors don't know what usually causes those plaques.

In some ways, Alzheimer's disease is still a mystery, much as it was 100 years ago.

Dr. Sam Gandy is a professor and director at the Farber Institute for the Neurosciences of Thomas Jefferson University in Philadelphia. Gandy is also chair of the Alzheimer Association's National Medical and Scientific Advisory Council.

When Will There Be a Cure?

OK, then, so, what do doctors and scientists know for sure about Alzheimer's?

Certainly, several things happen in the brain before the first signs of Alzheimer's appear:

Levels of a key brain chemical plummet: The technical name for this substance is acetylcholine.

Levels of two substances rise: The technical names are amyloid and tau.

Standard lab animals never develop Alzheimer's unless they are given a gene with a mutation that causes human Alzheimer's. Then, they develop some, but not all, features of the human illness.

Doctors know for sure they can cure mice with some of the features of Alzheimer's.

Some people with Alzheimer's get a little better for a little while with medicines like Aricept, Exelon and Razadyne. Those medicines help the brain compensate for the loss of acetylcholine.

These medicines will not stop the progression of the basic cause of Alzheimer's.

Alzheimer's develops in people with Down's syndrome and in people with rare genetic mutations.

Knowing anything "for sure" about Alzheimer's is a great leap forward, especially considering that the very first Alzheimer gene was only discovered 15 years ago!

But, what does the flip side look like? What do experts not know that we wish we did know?

Experts do not know for sure:

What causes the most common form of Alzheimer's.

Whether the medicines that work for mouse models will work for humans.

When Alzheimer's begins.

Who has Alzheimer's until the brain is examined under a microscope, which usually is only done after death, during an autopsy. It is technically possible to examine the brain while a person is still alive, but because Alzheimer's disease isn't treatable, that isn't a justifiable thing to do.

Exactly how to recommend diet and lifestyle modifications that will definitely lower a person's risk for Alzheimer's.

If or how rapidly brain function will decline once the very first memory change is noticed by someone or by his or her family.

Dr. Sam Gandy is a professor and director at the Farber Institute for the Neurosciences of Thomas Jefferson University in Philadelphia. Gandy is also chair of the Alzheimer Association's National Medical and Scientific Advisory Council.

Understanding Progress

How are doctors moving forward? What is being done to get the information to treat or prevent Alzheimer's?

Medicines and vaccines that work in mouse models are being tested in people with Alzheimer's. More than 100 Alzheimer's trials are listed at www.clinicaltrials.gov as being open for enrollment.

Local chapters of the Alzheimer's Association (www.alz.org) are now assisting patients to find details on trials in your area.

The very first brain scans have been developed with the promise of diagnosing and/or predicting Alzheimer's so that doctors can test new medicines at the very earliest stages of the disease. These tests undergo quality control as quickly as possible so that they can hopefully become widely available.

President Bush has cut Alzheimer's research for the first time in history. Each research study that initially asked for government funding now has less than a one in 10 chance for success.

Reconnecting With the Original Dr. Alzheimer

"So," doctors might say to Alzheimer if he were teleported here to the present.

"A hundred years have passed since you told us about your patient, Augusta. And in 100 years, we have learned so much about your disease, but we have also learned so little."

"Do you think the drugs we are currently testing will be effective? Were we right to bet on the genetic forms of Alzheimer's to teach us how to treat common forms of the disease? And will our research enterprise survive or collapse?"

The professor might take a few draws on his pipe and say, "Some things change over 100 years. Some things do not. These are the same questions that scientists in my day thought about, too -- all day, every day."

"But, Dr. Alzheimer," doctors might say. "Do you realize that dementia alone will soon consume our country's entire health-care budget? That there will be no money left for people with any other diseases?"

With a knowing glance and an air of enthusiastic determination, Alzheimer might once again set himself to the task.

"What are we waiting for? We have work to do!" he might say, and away the doctors would all go to the bedside, where Alzheimer would pick up where he left off, trying to unravel the secrets of a disease that still baffles and frustrates us.

Dr. Sam Gandy is a professor and director at the Farber Institute for the Neurosciences of Thomas Jefferson University in Philadelphia. Gandy is also chair of the Alzheimer Association's National Medical and Scientific Advisory Council.